JPH0610148B2 - Cycloalkyl alkynes - Google Patents

Description

Detailed Description of the Invention

The present invention relates to cycloalkylalkynes useful as intermediates in carotenoid synthesis.

Cycloalkylalkynes provided by the present invention have the general formula

[0003]

[Chemical 2]

In the formula, R ² represents hydrogen or hydroxy, R ³ represents hydroxy or ═CH—CH ₂ —OH, R ⁴ represents —CO—OR ⁶ ′ or —CO—R ⁶ ″, and R ⁶ 'represents an alkyl, and R ⁶ "represents an aryl or alkyl aryl, in which a compound represented.

According to the invention, the compounds of formula I above are R
General formula by cleavage of ⁴ OH

[0006]

[Chemical 3]

Wherein R ² and R ³ have the meanings given above,
Can be converted to a compound represented by

The terms "alkyl", "aryl" and "alkylaryl" include alkyl, aryl and alkylaryl groups preferably containing up to 10 carbon atoms. Examples of these groups are methyl, ethyl, phenyl, tolyl and the like.

According to the invention, it has been found that the compounds of the formula I can be converted into the pure compounds of the formula II under relatively mild conditions and in good yields.

The preparation of the compounds of the formula II according to the invention can be carried out in a manner known per se by cleaving the R ⁴ OH in the compounds of the formula I by heating and / or in the presence of a catalyst. Suitable catalysts are, for example: a) (eg imidazole,
1,2,4-triazole, aniline), b) salts of strong acids (preferably acids with pKa <1) with organic nitrogen bases, especially chlorides, bromides and tosylates (eg pyridinium p-tosylate), c) phosphonium salts ( For example triphenylphosphonium chloride or bromide), d) acids, preferably strong acids with pKa <1 [eg toluenesulfonic acid, Amberlys.
t) A 15 ^R (Fluka AG), hydrochloric acid, sulfuric acid], e) trialkylchlorosilane (eg trimethylchlorosilane), f) lithium salt, eg strong (pKa)
<1) Lithium salt of acid (for example, lithium chloride, lithium perchlorate, lithium tetrafluoroborate), and g) Palladium- (O) catalyst (for example, by addition of palladium acetate).

The reaction temperature depends in particular on the meaning of R ⁴ and whether the reaction is carried out in the presence or in the absence of a catalyst. The required reaction temperature is generally below 200 ° C .; however, in some cases the cleavage of R ⁴ OH also occurs at room temperature.
Pressure is not critical. Therefore, this reaction is preferably carried out at atmospheric pressure.

The conversion of compounds of the formula I into compounds of the formula II according to the invention is preferably carried out in inert organic solvents such as ethers, alcohols, nitriles, amides or saturated, aromatic or chlorinated hydrocarbons. Done. Examples of preferred solvents are diethyl ether, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, methanol, acetonitrile, dimethylformamide, hexane, toluene, benzene, xylene, methylene chloride, dichloroethane.

The process provided by the present invention can be carried out in the presence or absence of a catalyst.
If the process is carried out in the presence of a catalyst, the catalyst can be used in catalytic amounts or higher. Preferred catalysts are organic nitrogen bases, salts of these bases and lithium salts.

A further preferred embodiment of the process provided by the present invention is that the compound of formula I in which R ³ represents the group ═CH—CH ₂ OH is a phosphonium salt, preferably an equimolar amount of triphenylphosphonium chloride or bromide or this It consists of reacting in the presence of the above amount. According to this embodiment, first the corresponding compound of formula II is formed, which is then directly converted to the corresponding phosphonium salt [ie the hydroxy group at R ³ is a phosphonium salt, for example -P (C ₆ H _{5) 3} ⁺ Cl ^- or _{-P (C 6 H 5) 3} + Br - is converted to].

According to the method provided by the present invention,
Preference is given to using compounds of the formula I in which R ² represents hydroxy.

The group represented by R ³ = CH-CH _2-
The double bond present in OH preferably has the trans configuration.

A particularly preferred group for R ⁴ in formula I above is the group —CO—CR ⁶ ′, especially where R ⁶ ′ is C _1- .
A group representing C ₆ -alkyl. A particularly preferred group is-
CO-OCH a ₃ and -CO-OC ₂ H _5. When R ⁴ in the above formula I represents the radical —CO—R ⁶ ″, it is in particular a radical in which R ″ is aryl (eg benzoyl).

In principle, preference is also given to compounds of the formula I in which the elemental hydrogen at the 6-position of the cyclohexyl ring and the radical R ⁴ O-- represent one another in the cis position (syn elimination).

A further preferred embodiment of the method provided by the present invention is the general formula

[0020]

[Chemical 4]

Wherein R ³ and R ⁴ have the meanings given above,
Of the compound of formula (I) or its optical antipode by cleavage of R ⁴ OH in the presence of a sterically hindered basic lithium compound to give a compound of the general formula

[0022]

[Chemical 5]

Wherein R ³ has the meanings given above and comprises conversion to the compound or its optical antipodes.

The term "sterically hindered basic lithium compound" has a steric hindrance on a basic group [group -O].
Nucleophilic attack on R ⁴
In order to avoid attack) and lithium-organic compounds derived from organic compounds having a pKa value of at least 9, preferably at least 11. Steric hindrance can be effected, for example, by branching or substitution at the carbon atom in the 1-position or by substitution at the ortho position of the benzene ring. Among these compounds, preferred are alkyllithium, lithium alkanolate, lithium phenolate, lithium alkylamide, etc., which satisfy the above-mentioned conditions, such as lithium tert. Butyrate,
Lithium 1,1-dimethylpentanolate, lithium 2,6-dimethylphenolate, lithium 2,6-di (tert.butyl) phenolate, lithium 2,6-
Dichlorophenolate, tert. Butyl lithium,
2,6-di (tert.butyl) phenyllithium and lithium diisopropylamide.

In this embodiment, preferably at least about 2 moles of lithium compound are used per mole of compound of Formula Ia (or its antipode). In a particularly preferred embodiment, about 2 to 3 molar equivalents of lithium compound are used, but larger amounts will not have any detrimental effect on the reaction.

The temperatures, pressures and solvents mentioned above in connection with the reaction of the compounds of the formula I are likewise applicable to this embodiment. However, this embodiment is preferably performed at a temperature of about 40 ° C to about 70 ° C. Saturated hydrocarbons and aromatic hydrocarbons are particularly preferred solvents.

This embodiment gives a high yield. Furthermore, R ³ =
Steric configuration of the double bonds present in R ³ when it represents a CH-CH ₂ -OH is maintained. In addition, this embodiment provides pure isomer compounds because generally only the compounds of formula I and their optical antipodes (but not the remaining stereoisomers) react well under the mild temperature conditions described above. It is particularly suitable for manufacturing.

R ³ in the above formula Ia is preferably a group =
It represents a CH-CH ₂ -OH. The double bond in this group is preferably present in the trans configuration. Preferred groups represented by R ⁴ is -CO-OCH _3, -CO-
It is OC ₂ H _5, and -CO-C ₆ H _5.

The compounds of formula I are new and also form part of the invention. This compound is prepared in a manner known per se, for example in the corresponding lithium alcoholate (compound of formula I in which R ⁴ represents lithium).
From the corresponding chloride, namely the formula Cl-CO-C
R ⁶ 'or Cl-CO-CR ⁶ "[wherein, R ^6' and R ^6" have the meaning given above] can be prepared by reaction of a compound of. The lithium alcoholate required for this reaction can be obtained by reacting the corresponding cyclohexanone with the corresponding alkynyl lithium in a manner known per se. The hydroxy groups (in R ³ ) which are additionally present in this case are preferably present in protected form. These protecting groups can optionally be eliminated before or after the introduction of the radical R ⁴ .

The conversion of the compound of formula II into carotenoids can be carried out in a known manner or in a manner known per se, for example by conversion into a water-soluble aldehyde or phosphonium salt, which is then subjected to a Wittig reaction. it can.

The present invention will be described in more detail with reference to the following examples.

[0032]

EXAMPLES Example 1 Ethyl (1S, 4R, 6R) -4-hydroxy-1- (3
10.14 g of -hydroxy-1-butynyl) -2,2,6-trimethylcyclohexyl carbonate were dissolved in 50 ml of hot dimethylformamide. This solution was treated with 1 g of pyridinium p-tosylate and the mixture was stirred in a preheated oil bath for 1.5 hours (oil bath temperature 90-93.
C, internal temperature about 79-82C). The mixture was then poured into 500 ml of semisaturated sodium chloride solution and extracted 3 times with 200 ml of diethyl ether each time. The organic phase was washed once with saturated sodium chloride solution, dried over sodium sulphate and evaporated. The crude product obtained (8.3 g) was chromatographed on silica gel with hexane / diethyl ether (volume ratio 1: 1). Thus, 5.9 g (83.3%) of (4R) -4- (4-hydroxy-2,2,6-trimethyl-1-cyclohexenyl) -3-butyn-2-ol was obtained.

Ethyl used as starting material (1S, 4R,
6R) -4-hydroxy-1- (3-hydroxy-1-
Butynyl) -2,2,6-trimethylcyclohexyl carbonate was prepared as follows: a) In a four-necked flask equipped with a magnetic stirrer, thermometer, dropping funnel and inert gasifier, 4R, 6R) -4
-Hydroxy-2,2,6-trimethylcyclohexanone was dissolved in a mixture of 40 ml anhydrous tetrahydrofuran and 20 mg pyridinium p-tosylate with 19.52 g under argon and then added to this solution at 15-20 ° C within about 20 min. 14.4 g of ether was added dropwise. The resulting solution A was processed as described in section c).

B) 3-butyne-2- in 80 ml of anhydrous tetrahydrofuran in a sulfonation flask equipped with stirrer, thermometer, dropping funnel riser and inert gasifier.
A solution of 23.5 g of yltrimethylsilyl ether was charged under argon, cooled to -30 ° C, and within 10 minutes at -30 ° C to 20 ° C, about 1.5 butyllithium in hexane.
The solution was added dropwise with 105 ml of a 6M solution. -1 for this mixture
Stir at 0 ° C. for a further 30 minutes and then cool again to −40 ° C. The resulting solution B was processed as described in section c).

C) Solution A was dissolved at -40 ° C within 10 minutes.
It was dripped at B. The mixture is stirred for a further 30 minutes, then
Treat with 15.7 ml of ethyl chloroformate and stir the mixture
While warming to room temperature within 1 hour. Then mix 0
Cool to ℃ and treat with 100 ml of 3N sulfuric acid with stirring.
And stirred at 0-5 ° C for an additional 30 minutes. Vinegar this mixture
It was diluted with 250 ml of ethyl acidate and the aqueous phase was separated. The water phase
It was back-extracted twice with 250 ml each of ethyl acetate. Tired of the organic phase
250 ml of sodium bicarbonate solution three times, and
Wash once with 250 ml of saturated sodium chloride solution,
Dried and dried over sodium sulfate. The desiccant is filtered off,
After concentrating the filtrate on a rotary evaporator (water bath temperature 50 ° C.), the crude
43.6 g of the product of
With hexane / diethyl ether (volume ratio 1: 1) above
Then, it was chromatographed. Fracture containing product
From Chillon, a total of 36.5 g (9
7.8%) ethyl (1S, 4R, 6R) -4-hydroxy
Ci-1- (3-hydroxy-1-butynyl) -2,2,6
-Trimethylcyclohexyl carbonate was obtained. Example 2 Magnetic stirrer, thermometer, reflux condenser and argon head pipe
In a two-necked flask equipped with a headpiece, imida
6.7 g of sol was added to triethylene glycol under argon.
Dissolve in 40 ml of dimethyl ether and add this solution in an oil bath
Heated to 195 ° C. Then triethylene glycol di
Ethyl in 15 ml of methyl ether (1S, 4R, 6R)
-4-hydroxy-1- (5-hydroxy-3-methyl
-3E-Pentene-1-ynyl) -2,2,6-trimethyl
The solution of 8.0 g of rucyclohexyl carbonate was heated to the internal temperature.
Dropwise at 188-190 ° C within 60 minutes. This mix
Store the same at the same temperature for another 30 minutes, then ice / water 200
poured into ml. Aqueous phase with 250 ml of diethyl ether each
Extracted twice. Combined ether phases with 100 ml of water each
Wash 4 times, dry over sodium sulfate, and spin at about 50 ° C.
Concentrate on inversion evaporator and then dry under high vacuum at room temperature for 3 hours.
Dried The crude product obtained (0.6 g) was treated with silica gel.
On diethyl ether / hexane (volume ratio 1: 1)
Chromatography, and thus a little yellowish
Oil of (4R) -5- (4-hydroxy-2,2,
6-trimethyl-1-cyclohexenyl) -3-methyl
-2-Penten-4-yn-1-ol 3.5 g (61.
4%) could be isolated (ratio 2E / 2Z = 91.
0: 4.7).

Ethyl used as a starting material (1S, 4R,
6R) -4-hydroxy-1- (5-hydroxy-3-
Methyl-3E-penten-1-ynyl) -2,2,6-trimethylcyclohexyl carbonate was prepared as follows: a) equipped with magnetic stirrer, thermometer, dropping funnel and inert gasifier. In a four-necked flask, (4R, 6R) -4
-Hydroxy-2,2,6-trimethylcyclohexanone 52.0 g of tetrahydrofuran under argon 65 ml
And 50 mg of pyridinium p-tosylate, and the solution was treated dropwise with isopropenyl methyl ether 48.0 g within 20 minutes at 15 to 20 ° C. The resulting yellowish solution A was directly processed as described in section c).

B) 5- (2-methoxy-2-propyl) oxy-3 in 50 ml of anhydrous tetrahydrofuran in a sulfonation flask equipped with stirrer, thermometer, dropping funnel riser and inert gasifier. A solution of 79 g of -methyl-3E-penten-1-yne was charged under argon and cooled to -20 ° C. This solution is -30 ℃ ~ 20 ℃
Butyllithium in hexane about 1.5 in less than 20 minutes
It was treated dropwise with 280 ml of a 6M solution and the resulting mixture was stirred for a further 30 minutes. The resulting orange solution B was directly processed as described in section c).

C) Solution B was treated dropwise with Solution A within 20 minutes at -15 ° C. and the mixture was stirred at room temperature for a further 30 minutes. The mixture is cooled to −20 ° C. and treated with 42 ml of ethyl chloroformate with stirring, then the mixture obtained is 1
Warm to room temperature over time. Then the mixture was diluted with 250 ml of diethyl ether and the aqueous phase was back-washed with 250 ml of diethyl ether. The organic phase was washed twice with 250 ml each of saturated sodium chloride solution, combined and dried over sodium sulphate. After filtering off the desiccant and concentrating the filtrate on a rotary evaporator (water bath temperature 50 ° C.), crude ethyl (1S, 4R, 6R) -4- (2-methoxy-2) was obtained as a brown-yellow oil.
-Propyl) oxy-1- [5- (2-methoxy-2-
Propyl) oxy-3-methyl-3E-pentene-1-
181.5 g of inyl] -2,2,6-trimethylcyclohexyl carbonate were obtained.

D) The brown-yellow oil obtained was dissolved in 450 ml of tetrahydrofuran and 50 ml of water (turbid solution), treated with 2 g of pyridinium p-tosylate and stirred for a further 20 minutes (clear solution). The brown-yellow oil solution was then treated with 2 g of solid potassium carbonate and evaporated on a rotary evaporator to constant weight (bath temperature 50 ° C.). The residue was diluted with 250 ml of diethyl ether and extracted with 250 ml of water. The aqueous phase is separated and 250 ml of diethyl ether
Back-extracted with. 25 organic phase saturated sodium chloride solutions each
It was washed twice with 0 ml, combined and dried over sodium sulfate. After filtering off the drying agent and concentrating the filtrate on a rotary evaporator (water bath temperature 50 ° C.), 140 g of crude product are obtained, which is taken up on silica gel in diethyl ether / hexane (volume ratio 1: 1). I went to chromatography. From the product-containing fraction, pure ethyl (1S, 4R, 6R) -4-hydroxy-1- (5-hydroxy-3-methyl-3E-penten-1-ynyl) -2,2 as a slightly yellowish oil was obtained. A total of 99.0 g (91.6%) of 6,6-trimethylcyclohexyl carbonate was obtained.

Example 3 In a two-necked flask equipped with a magnetic stirrer, a reflux condenser and an argon headpiece, 4.4 g of imidazole was dissolved in 50 ml of triethylene glycol diethyl ether under argon and the solution was placed in an oil bath. Heated to 195 ° C.
Next, 10 ml of triethylene glycol dimethyl ether
1- (5-hydroxy-3-methyl-3E- in
A solution of 5 g of pentene-1-ynyl) -2,2,6-trimethylcyclohexyl carbonate was added at an internal temperature of 185-1.
It was added dropwise at 90 ° C. within about 20 minutes. The mixture was stored at the same temperature for a further 1 hour and then poured into 200 ml ice / water. The aqueous phase was extracted twice with 250 ml of diethyl ether each time. The combined ethereal phases were washed 4 times with 100 ml of water each time, dried over sodium sulphate, concentrated on a rotary evaporator at about 40 ° C. and then dried under high vacuum at room temperature for 2 hours.
The crude product obtained (3.6 g) was chromatographed on silica gel with diethyl ether / hexane (volume ratio 1: 1). From the product-containing fraction, 2.1 g (59%) of 5- (2,6,6-trimethyl-1-cyclohexenyl) -3-methyl-2-penten-4-yn-1-ol as a slightly yellowish oil was obtained. 0.5%) was obtained. (Ratio 2E / 2Z = 98.8: 0.6).

Ethyl 1- (5-hydroxy-3-methyl-3E-penten-1-ynyl) used as starting material
-2,2,6-Trimethylcyclohexyl carbonate was prepared as follows: a) In a sulfonation flask equipped with stirrer, thermometer, dropping funnel and argon headpiece, 5- (2-methoxy) was used. 2-Propyl) oxy-3-methyl-3E-penten-1-yne 115.1 g and tetrahydrofuran 90 ml are charged, the mixture is cooled to -25 ° C. and butyl lithium in hexane at this temperature is added within 20 minutes. 1.
Dropwise treatment with 6M solution. This mixture is further stirred at 0 ° C for 15
Stir for minutes, then cool to -10 ° C and within 15 minutes at this temperature 2,2,6-trimethylcyclohexanone 72.9
Dropwise treatment with g. The mixture is then warmed to room temperature and further 2
Stir for hours. The mixture was cooled to 0 ° C., treated dropwise with 67.5 ml of ethyl chloroformate at this temperature within 15 minutes, allowed to warm to room temperature and stirred for a further 1.5 hours. Then the mixture was poured into 1 l of saturated sodium hydrogen carbonate solution and extracted twice with 1 l of diethyl ether each time. The organic phase was washed with 1 l of deionized water, dried over sodium sulphate, the desiccant was filtered off and the filtrate was concentrated under vacuum on a rotary evaporator (bath temperature approx. 45 ° C.). From the residue under high vacuum at a bath temperature of 60 ° C. for 1 hour, 5- (2-methoxy-2-
Propyl) oxy-3-methyl-3E-pentene-1-
The inn was removed. Crude ethyl 1- [5- (2-methoxy-2-propyl) oxy-3-methyl-3E-penten-1-ynyl] -2,2,6-trimethylcyclohexylcarbonate 232.1 g (117.3%) ) Is obtained,
This was directly processed without further purification.

B) 105.5 g of the crude product obtained as described in section a) above is dissolved in 630 ml of tetrahydrofuran in a sulfonation flask equipped with a stirrer, thermometer and argon headpiece. This solution was treated with 105 ml of deionized water and 5.25 g of pyridinium p-tosylate and the mixture was stirred at room temperature for a further 30 minutes. This mixture is added to a saturated sodium hydrogen carbonate solution 750
It was poured into 3 ml and extracted with 600 ml of diethyl ether three times. The organic phase is a semi-saturated sodium hydrogen carbonate solution 750 m.
Washed with l, dried over sodium sulphate, filtered off the drying agent and concentrated the filtrate under vacuum on a rotary evaporator (bath temperature approx. 45 ° C.). After drying under high vacuum, the crude product 84.
8 g (116.9%) were obtained, which was chromatographed on silica gel with hexane / diethyl ether (2: 1 by volume). Thus 5- (2,
2.3 g of 6,6-trimethyl-1-cyclohexenyl) -3-methyl-2-penten-4-yn-1-ol
(4.5%) and ethyl 1- (5-hydroxy-3-methyl-3E-penten-1-ynyl) -2,2,6-trimethylcyclohexyl carbonate 53.6 g (73.9).
%)was gotten.

Example 4 In a sulfonation flask equipped with a stirrer, thermometer, dropping funnel, reflux condenser and inert gasifier, tert.
16 ml butanol and 20 ml anhydrous toluene were charged under argon and cooled to -25 ° C. This solution-
Within 10 minutes at 30 DEG C. to -20 DEG C., 25 ml of a 1.56 M solution of butyllithium in hexane were added dropwise and the mixture was stirred for a further 30 minutes while cooling. The lithium tert. About 2 in butyrate solution
(1S, 4R, 6R) in 120 ml of anhydrous toluene at 0 ° C
A solution of 14.4 g of -4-hydroxy-1- (5-hydroxy-3-methyl-3E-penten-1-ynyl) -2,2,6-trimethylcyclohexylbenzoate was added at once. Carefully transfer the resulting suspension to 65 with an oil bath.
Heat to ℃ and stir at this temperature for 1.5 hours. afterwards,
The mixture was poured into 150 ml ice / water. The aqueous phase was separated and extracted twice with 150 ml of diethyl ether each. The organic phase is washed with 150 ml of saturated sodium chloride solution, combined and
It was then dried over sodium sulphate and concentrated on a rotary evaporator at about 40 ° C., then the residue was dried under high vacuum at room temperature for 1 hour. The crude product obtained (12.0 g) was applied onto silica gel with diethyl ether / hexane (volume ratio 1: 1).
Then it was chromatographed. From the product-containing fraction, (4R) -5-as yellowish crystals.
(4-Hydroxy-2,2,6-trimethyl-1-cyclohexen-1-yl) -3-methyl-2E-pentene-
A total of 7.5 g (80%) of 4-in-1-ol was obtained (purity 98.8%, 2Z isomer content 1.1%).

Used as starting material (1S, 4R, 6R)
-4-Hydroxy-1- (5-hydroxy-3-methyl-3E-penten-1-ynyl) -2,2,6-trimethylcyclohexylbenzoate was prepared as follows: a) () 4R, 6R)-
4-hydroxy-2,2,6-trimethylcyclohexanone 16.4 g and pyridinium p-tosylate 30 mg
Solution was treated dropwise with argon within 15 minutes at 15-20 ° C. with 16.0 g of isopropenyl methyl ether.

B) A solution of 27 g of 5- (2-methoxy-2-propyl) oxy-3-methyl-3E-penten-1-yne in 30 ml of anhydrous tetrahydrofuran was cooled to -20 ° C under argon and then 10 at -30 ℃ to 20 ℃
Within minutes, it was treated dropwise with 90 ml of a 1.56 M solution of butyllithium in hexane and the mixture was stirred for a further 30 minutes.

C) The solution obtained as described in section b) above is treated dropwise at -15 ° C. within 15 minutes with the solution prepared as described in section a) above and the mixture is treated. The mixture was stirred at room temperature for another hour. The mixture is cooled to -10 ° C and treated with 18.6 ml of benzoyl chloride with stirring,
It was then stirred overnight (18 hours) at room temperature. Then the mixture was poured into 200 ml of saturated sodium hydrogen carbonate solution, the aqueous phase was separated and back-extracted twice with 300 ml of diethyl ether each. The organic phase is washed twice with 250 ml each of saturated sodium chloride solution, concentrated, dried over sodium sulphate and the desiccant is filtered off. The filtrate was rotary evaporated (water bath temperature 40
C) and then crude (1S, 4
R, 6R) -4- (2-Methoxy-2-propyl) oxy-1- [5- (2-methoxy-2-propyl) oxy-3-methyl-3E-penten-1-ynyl] -2,2 ,
6-Trimethylcyclohexylbenzoate is obtained.

D) The brown-yellow oil obtained was dissolved in 400 ml of tetrahydrofuran and 20 ml of water (turbid solution), treated with 1 g of pyridinium p-tosylate and stirred for a further 15 minutes (clear solution). Then the mixture was poured into 200 ml of saturated sodium hydrogen carbonate solution, the aqueous phase was separated and extracted twice with 300 ml of diethyl ether each.
The organic phases were combined, dried over sodium sulphate and the desiccant was filtered off. After concentrating the filtrate on a rotary evaporator (bath temperature 40 ° C.), 51.3 g of crude product are obtained, which on silica gel is diethyl ether / hexane (volume ratio 2:
Chromatography according to 1). From the product-containing fraction, a pure yellow (1S,
4R, 6R) -4-Hydroxy-1- (5-hydroxy-3-methyl-3E-penten-1-ynyl) -2,2,
Total of 6-trimethylcyclohexyl benzoate 32.
2 g (86.1%) were obtained.

Example 5 In a sulfonation flask equipped with a stirrer, a thermometer, a dropping funnel, a reflux condenser and an inert gasifier, tert.
40 ml butanol and 50 ml anhydrous toluene were charged under argon and cooled to -25 ° C. This solution-
Within 30 minutes at 30 ° C. to 20 ° C., 130 ml of a 1.56 M solution of butyllithium in hexane were added dropwise and the mixture was stirred for a further 30 minutes while cooling. The lithium tert. To a solution of butyrate at 6 ° C in ethyl acetate (1S, 4R,
6R) -4-hydroxy-1- (5-hydroxy-3-
A solution of 32.4 g of methyl-3E-penten-1-ynyl) -2,2,6-trimethylcyclohexyl carbonate (prepared according to Example 2) was added in one portion. The mixture was carefully heated to 55 ° C. with an oil bath and stirred at this temperature for 30 minutes. Then mix the mixture with ice / water 40
Poured to 0 ml. Separate the aqueous phase and use 3 portions of diethyl ether.
It was extracted twice with 00 ml. The organic phase is washed with 300 ml of saturated sodium chloride solution, combined, dried over sodium sulphate and concentrated on a rotary evaporator at about 40 ° C., then the residue is dried under high vacuum at room temperature for 5 hours. . Thus (4R)
-5- (4-hydroxy-2,6,6-trimethyl-1-
Cyclohexenyl) -3-methyl-2-pentene-4-
23.9 g of a yellow-orange crystalline product of in-1-ol (containing 1.4% of 2Z isomer and 90.5% of 2E isomer).
(102.1%) was obtained, which was chromatographed on silica gel with diethyl ether / hexane (volume ratio 1: 1). From the product-containing fraction, (4R) -5- (4-hydroxy-2,6,6-trimethyl-1-cyclohexene-) was obtained as yellowish crystals.
1-yl) -3-methyl-2E-penten-4-yn-
1-ol (purity 98.0%, 2Z isomer content 0.5%)
A total of 19.9 g (85%) was obtained.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Erich Widmer Switzerland 4142 Miyun Hengsyu Tyne Mitsu Terbeek 47

Claims (1)

[Claims] 1. A general formula: In the formula, R ² represents hydrogen or hydroxy, R ³ represents hydroxy or ═CH—CH ₂ —OH, R ⁴ represents —CO—OR ⁶ ′ or —CO—R ⁶ ″, and R ⁶ ′ represents A compound of the formula: alkyl, and R ⁶ ″ represents aryl or alkylaryl.